Is there a role for surgery in metastatic colorectal cancer? Alan E. Harzman, MD Assistant Professor - Clinical Set B1 – Title Slide

Yes. Large Projection – Content Slide Thank you for your time.

Outline Obstruction Overview of colorectal metastasis Solid organ metastasis Peritoneal metastasis Set B1 – Content Slide

Obstruction Large Projection – Content Slide

Obstruction 8-29% of CRC patients at initial presentation 77% left-sided, 23% right-sided Set B1 – Content Slide

Interventions Low-residue diet and start chemotherapy or radiation Laser therapy to open lumen (for distal lesions) Fulguration Stent Diverting stoma Resection +/- anastomosis But not above another lesion Set B1 – Content Slide

Overview Large Projection – Content Slide

Sites of Colorectal Metastasis Peritoneum Liver Portal circulation Lung Ovary Bone Brain Incisions Spleen Other Set B1 – Content Slide

Sites of Possible Ectomies Peritoneum Liver Lung Ovary Bone Brain Incisions Spleen Other Set B1 – Content Slide

Basic Elements of a Good Metastasectomy Long disease-free interval Slow-growing disease Good functional status Good exit strategy This is not like a war. We can’t raise health like the government can raise taxes Set B1 – Content Slide

Lung as an example Large Projection – Content Slide

Factors in Lung Resection Ideally, a solitary metastasis. Possibly multiple nodules in one lung, or a single nodule in each. Primary site is controlled No other evidence of metastasis Patient can tolerate resection Set B1 – Content Slide

Survival After Lung Resection Operative mortality – 3% 3-year survival – 45-78% 5-year survival – consistently around 30% Set B1 – Content Slide

Liver Large Projection – Content Slide

Liver Metastasis 60% of the 150,000 new US cases of CRC yearly will eventually develop liver metastasis. 10% of those people will be candidates for curative-intent hepatic surgery 5-10 month survival untreated 24-23% 3-year and 2-8% 5-year survival of people who might have been surgical candidates in retrospect Set B1 – Content Slide

Surgical Options for Hepatic Metastasis Hepatectomy Hepatic Artery Infusion Radio frequency ablation Cryoablation Set B1 – Content Slide

Hepatectomy Mortality – 5% or less Morbidity – 20-50% 5-year survival – 25-40% 10-year survival – 20-26% Median survival 24-46 months Set B1 – Content Slide

Hepatectomy Not for Two-thirds will recur Extra-hepatic disease Except maybe pulmonary or anastomotic Incomplete resectability Two-thirds will recur Set B1 – Content Slide

aka peritoneal carcinomatosis Peritoneum aka peritoneal carcinomatosis Large Projection – Content Slide

'Omental cake' in a patient with peritoneal carcinomatosis arising from appendiceal cancer. Glockzin et al. World Journal of Surgical Oncology 2009 7:5   doi:10.1186/1477-7819-7-5

Peritoneal Carcinomatosis - Mechanisms Seeding from T4 CRC Extravasation with perforation of the tumor Tumor perforation at operation Leakage of tumor cells from lymphatics or veins at time of operation Set B1 – Content Slide

Peritoneal Carcinomatosis 10-15% of patients at CRC presentation 25-35% of CRC recurrences Survival 6-8 months without therapy Can lead to malignant ascites or malignant bowel obstruction Set B1 – Content Slide

Peritoneal Surface Malignancy Group Increased probability of complete macroscopic cytoreduction in CRC ECOG performance status <=2 No extra-abdominal disease Up to three, small, resectable hepatic mets No biliary obstruction No ureteral obstruction Small bowel – no gross mesenteric disease Small-volume disease in gastro-hepatic ligament Set B1 – Content Slide

(Cotte et al., 2009)

Pseudomyxoma Peritonei Often diagnosed with acute appendicitis, abdominal swelling or ovarian mass Minimal operating should be done at the time of diagnosis Confusing pathology Set B1 – Content Slide 25

Factors in Pseudomyxoma Peritonei Tumor grade Extent of mesenteric invasion Liver metastasis Age Set B1 – Content Slide

Cytoreductive Surgery Peritonectomy (parietal and visceral) Greater omentectomy Lesser omentectomy Splenectomy Cholecystectomy Liver capsule resection Small bowel resection Large bowel/rectal resection Hysterectomy Oopherectomy Cystectomy Omphalectomy – for invasion of umbilicus Set B1 – Content Slide

Omphalectomy in a patient with umbilical tumor infiltration. Glockzin et al. World Journal of Surgical Oncology 2009 7:5   doi:10.1186/1477-7819-7-5

(Cotte et al., 2009)

(Cotte et al., 2009)

Intraperitoneal Chemotherapy Mortality – 5% Morbidity – 35% Various agents, especially mitomycin C Hyperthermia Increased chemotherapeutic activity Direct effects – protein denaturation, induction of apoptosis, inhibition of angiogenesis High local dose with less systemic toxicity Complete gross resection is most important 5-year survival – 27-54% Set B1 – Content Slide

Schematic diagram of HIPEC procedure. Glockzin et al. World Journal of Surgical Oncology 2009 7:5   doi:10.1186/1477-7819-7-5

Cytoreductive Surgery and IPHP Morbidity 25-41% Surgical – Anastomotic leak, ileus, wound infection, bleeding, thrombosis, embolism Chemotherapeutic – Leukopenia, anemia, thrombopenia, heart, liver, renal Mortality 0-8% Shows individual and institutional learning curves Set B1 – Content Slide

Survival With cytoreductive surgery and intraperitoneal hyperthermic chemotherapy Survival 15-32 months 28-60 months with complete macroscopic cytoreduction With systemic chemotherapy alone (5-FU/leucovorin) 12-14 months Set B1 – Content Slide 34

Quality of Life Acceptable functional status returns at 3-6 months 32% depressed at surgery, and 24% one year afterward Role and social functioning may remain impaired in long-term functioning Set B1 – Content Slide 35

Summary There are a wide variety of options for surgical therapy in metastatic colorectal cancer. Most are very invasive and somewhat risky. However, they all extend meaningful life in properly selected patients. Those patients may be the minority of patients with metastatic colorectal cancer, but with 150,000 new cases a year, there are many of them out there. Set B1 – Content Slide 36

References Berri, RN, & Abdalla EK. (2009). Curable metastatic colorectal cancer: recommended paradigms. Current Oncology Reports, 11, 200-208. Cotte, E, Passot, G, Mohamed, F, Vaudoyer, D, & Glehen, O. (2009). Management of peritoneal carcinomatosis from colorectal cancer. The Cancer Journal, 15(3), 243-248. Glockzin, G. (2009). Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World Journal of Surgical Oncology, 7(5). Gordon, PH, & Nivatvongs, S. (2007). Principles and practice of surgery for the colon, rectum, and anus. Third edition. New York: Informa Healthcare. Moran, B, Baratti, D, Yan, TD, Kusamura, S, & Deraco, M. (2008). Consensus statement on teh loco-regional treatment of appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei). Journal of Surgical Oncology, 98, 277-282. Wolff, BG, Fleshman, JW, Beck, DE, Pemberton, JH, & Wexner, SD. (2007). The ASCRS textbook of colon and rectal surgery. New York: Springer. Set B1 – Content Slide

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